NM_007194.4:c.953G>A (p.Arg318His) is a missense variant in CHEK2 exon 9, located within the kinase domain. The variant has been observed at extremely low frequency in population databases (gnomAD v2.1: 13/282,864 alleles, AF=0.0046%; v4.1: 73/1,613,934 alleles, AF=0.0045%), consistent with PM2 at supporting level.¹ Computational in silico tools uniformly predict a benign effect: REVEL score 0.061, BayesDel score -0.127872, and SpliceAI max delta 0.00, supporting BP4 at supporting level.² Dong et al. (2003, PMID:12533788) identified this variant in 1 of 94 early-onset prostate cancer cases and 0 of 423 unaffected controls; it was not found in familial prostate cancer cases, and the single observation does not achieve statistical significance for PS4.³ ClinVar reports this variant as Uncertain Significance (15 clinical laboratories) and Likely Benign (1 laboratory). No expert panel has classified this variant.⁴ With PM2 (supporting pathogenic) and BP4 (supporting benign) applied, the evidence is balanced. The variant is classified as Variant of Uncertain Significance (VUS). Additional functional data (BS3/PS3) and case-control studies (PS4) are needed to resolve the classification.